Disinfectant solution based on sodium hypochlorite, and process for preparing it

ABSTRACT

Sodium hypochlorite disinfectant solution having a pH of between 10.1 and 10.7 and comprising from 0.021 to 5.76% (w/v) of sodium hypochlorite and, relative to the said amount of sodium hypochlorite, not more than 2% of sodium chlorate.

The present invention relates to a disinfectant solution based on sodiumhypochlorite and to a process for preparing it.

Throughout the present description and the claims, unless otherwisespecified, the term “solution” always refers to an aqueous solution.

The bactericidal properties of sodium hypochlorite solutions have beenknown since 1820. Above all in France, in the period of the First WorldWar, they were also widely used for the medical treatment of warinjuries.

Even today, they are widely used as disinfectants for environments,surfaces, surgical instruments, various objects and injures.

The disinfectant activity of sodium hypochlorite solutions depends to alarge extent on the bactericidal activity of hypochlorous acid and,thus, on its presence in the solutions.

The efficiency of the activist is influenced by the temperature, thecontact time, the type and concentration of the micro-organisms and,above all, the pH. Since the dissociation constant of hypochlorous acidto 25° C. is pKa=7.49, it results that when the hypochlorite solutioncomes into contact with bodily fluids, the pH is modified and tends toapproach neutrality, and thus the ratio between the ionized species andneutral species tend to become equal. Now, although hypochlorite is abland disinfectant compared with hypochlorous acid, it acts as areserve.

EP-A-0 471 129 relates to a solution of sodium hypochlorite which isuseful as an antiseptic. The solution contains sodium hypochlorite in aquantity sufficient for 4 to 6 grams per liter of active chlorine, a pHregulator In a quantity sufficient to yield a pH greater than 10 andless than or equal to 10.5 and purified water in a quantity sufficientto yield 1 liter of solution.

U.S. Pat. No. 5,624,636 aims at improving the disinfection of dentalimpressions following removal from the patient's mouth and beforeentering the dental laboratory to prevent contamination. It Involves theuse of a pH-adjusted hypochlorite solution, which is highly effective inkilling microorganisms, and also relatively inexpensive. Thedisinfectant solution causes no damage to the impression, no loss ofaccuracy, and does not destroy the details on the impression surface.The solution has a pH of from 9 to 11 and has a sodium hypochloritecontent of from 0.05% to about 1.05%.

U.S. Pat. No. 4,440,334 discloses a germicidal solution for sanitizingthe human epidermis without irritation. The solution is a homogeneousblend of glycerol, sodium hypochlorite, inert ingredients, soft water,scented oil, and isopropyl alcohol, having a pH of 9.8 to about 10.1.The solution may be applied to a towelette and sealed in a hermeticallysealed pouch for later use.

One of the problems associated with sodium hypochlorite disinfectantsolutions is that their composition cannot be predetermined at willsince the industrial methods for producing hypochlorite give solutionsin which the sodium hypochlorite is accompanied by side products andstarting materials. Thus, since the said industrial solutions are theonly sources of hypochlorite that are available for preparing the saiddisinfectant solutions, the said disinfectant solutions will necessarilyalso contain a certain amount of the said side products and startingmaterials already present in the industrial hypochlorite solution used.

The production of sodium hypochlorite is based on the dismutation ofmolecular chlorine in sodium hydroxide solution.

This reaction, also known as “chlorination of alkali”, proceedsaccording to the following reaction scheme (I):Cl₂+2 NaOH→NaClO+NaCl+H₂O  (I)

The industrial process more commonly involves the addition of chlorineto an excess of sodium hydroxide.

Solutions containing about 15.70–20.93% (w/v) of sodium hypochlorite[equivalent to 15.00–20.00% (w/v) of active chlorine] are thus obtained,also containing a substantially equivalent amount of sodium chloride andan excess of free bases, generally less than 1% (expressed as NaOH),which gives a pH of about 12.5–13.5 and acts as stabilizer.

Throughout the present description and the claims, this type of solutionwill be referred to as a concentrated solution.

Concentrated sodium hypochlorite solutions have various industrial usesand, when used in unmodified form or suitably diluted, are also used fordisinfecting articles. However, the said solutions cannot be used inunmodified form for clinical and/or veterinary disinfection since theyare not tolerated by the skin or mucous membranes.

Moreover, its high pH value also prevents the formation of hypochlorousacid.

Hypochlorite disinfectant solutions are therefore prepared by diluting aconcentrated solution with added mineral salts which act as buffers toreduce its pH and thus improve its tolerability and bactericidalactivity.

In particular, typical disinfectant solutions for topical use are asfollows:

-   -   Dakin's solution (French Pharmacopoeia 8th edition, p. 1059)        containing about 0.5% sodium hypochlorite, the same percentage        of sodium chloride, 1.5% sodium bicarbonate and 1 mg/100 ml of        potassium permanganate; and    -   the skin disinfecting solution described in the US Pharmacopoeia        (USP 24, p. 1535), which contains 0.02–0.032% sodium        hypochlorite, 1.02 g/l monobasic sodium phosphate, 17.61 g/l        dibasic sodium phosphate and has a pH of between 7.8 and 8.2.        Although it is not mentioned by the USP, since this solution is        prepared from a concentrated sodium hypochlorite solution, it        also contains at least 0.02–0.032% sodium chloride.

However, reducing the pH of these solutions has the drawback of reducingthe stability of the sodium hypochlorite and so, depending on theircomposition, these solutions can only be stored from a minimum of a fewdays to a maximum of a few months (S. F. Bloomfield, T. J. Sizer,“Pharm. J. (1985), 153–157).

The said disinfectant solutions must therefore be prepared by the userat the time of use or slightly beforehand.

Specifically, even if stored with care, the abovementioned sodiumhypochlorite disinfectant solutions obtained by diluting a concentratedsolution with added buffers undergo a spontaneous decomposition whichproduces sodium chlorate, sodium chloride and small amounts of sodiumchlorite.

The formation of sodium chlorate and sodium chlorite also has thedrawback that these products have toxicological properties (DrinkingWater and Health, Disinfectants and Disinfectant By-products. volume 7,National Academy Press, Washington, D.C., 1987) which are such thatregulations have been drawn up therefor (Priority list of substancesthat may require regulation under the safe drinking water act; EPA,1991, (56), 9, 1470–1474, EPA 40 CFR part 9 141, 142 National PrimaryDrinking Water Regulations: Disinfectant and Disinfection Byproduct,Final Rule, Dec. 16, 1998).

The only known method for preparing relatively dilute sodiumhypochlorite solutions that do not have the drawbacks of the solutionsobtained by diluting a concentrated solution with added buffers is thatof the electrolysis of sodium chloride solutions in diaphragm-freeelectrolytic cells so as to allow the products that are gradually formedby the electrolysis to react together. The dilute sodium hypochloritedisinfectant solutions thus obtained contain an excess of sodiumchloride and have a pH of between 10 and 10.5.

These solutions, subsequently diluted without pH correction or with thepossible addition of small amounts of pH correctors, are well toleratedby the skin and mucous membranes. In addition, they are stable for atleast two years and can therefore be dispensed in pharmacies.

Typical examples of possible pH correctors are sodium bicarbonate,sodium tetraborate and monobasic and dibasic sodium phosphate mixtures.

A disinfectant solution of this type has been sold for many years underthe brand name AMUCHINA™ and has the following composition:

sodium hypochlorite: 1.15% (w/v), equivalent to 1.1% active chlorine;sodium chloride: 18% (w/v); sodium chlorate: 17–26%, relative to theabovementioned amount of sodium hypochlorite; pH 10–10.5.

Hereinbelow, the sodium hypochlorite solutions obtained by theelectrolysis of sodium chloride in diaphragm-free electrolytic cellswill be referred to as “electrolytic solutions”.

Despite the abovementioned advantages, electrolytic solutions contain alarge excess of sodium chloride and this may be a drawback in certaintypes of application such as, for example, rendering water fit forconsumption.

The sodium chlorate contained arises due to the fact that, besides thespontaneous decomposition, a secondary reaction of anodic oxidation ofthe hypochlorite is associated with the primary electrolytic reaction,to a certain extent (6ClO⁻+3H₂O→2ClO₃ ⁻+4Cl⁻+6H⁺+3/2O₂+6e⁻).

However, the main drawback of electrolytic solutions consists of thehigh costs of the plants required to produce them and of the costsincurred in their management.

In addition, the electrolytic method cannot be used to producerelatively concentrated solutions [>3% (w/v)] since this would initiatesecondary electrolytic reactions which would lead to a reduction in theyield and, above all, to the production of excessively high levels ofsodium chlorate, thus harming the quality of the solutions.

Therefore, notwithstanding the many attempts made over more than acentury, an inexpensive method for preparing a sodium hypochloritedisinfectant solution that is stable for at least two years, does notcontain an excess of sodium chloride, has high bactericidal activity andis well tolerated by the skin and mucous membranes has still not beenfound.

Hitherto, these objectives have been considered as mutually incompatiblesince, as already seen, an alkaline pH ensures the stability but has aharmful effect on the tolerability by the skin and mucous membranes andreduces the bactericidal power. On the other hand, at neutral pH, thebactericidal power is high, but stability is low.

French patent 2 593 704 describes a stabilized and dilute 0.5% sodiumhypochlorite solution in which the stabilization is achieved by addingan amount of monosodium phosphate which is sufficient to lower the pH toa value of 9.6–10. According to the said document, the abovementioneddisinfectant solution is well tolerated by the skin but has a stabilityof only six months.

Now, it has been found, surprisingly, that the dilution of aconcentrated sodium hypochlorite solution and the addition of dilutehydrochloric acid until the pH is 10.1–10.7 makes this solution welltolerated by the skin and mucous membranes without reducing itsstability, without forming appreciable amounts of sodium chlorate andwithout the addition of other ionic solutes.

Typically, a sodium hypochlorite disinfectant solution thus obtained hasthe following characteristics:

sodium hypochlorite: 0.021–5.76% (w/v), equivalent to 0.020–5.50% (w/v)of active chlorine; sodium chlorate: 1.7% relative to the abovementionedamount of sodium hypochlorite; water: qs 100 ml pH 10.1–10.7

This solution is novel since it differs from the other knownhypochlorite disinfectant solutions, obtained by diluting a concentratedsolution with added buffers, in terms of the pH value and the absence ofbuffers. In addition, it differs from electrolytic solutions in terms ofthe levels of sodium chlorate.

In a first aspect thereof, the present invention therefore relates to asodium hypochlorite disinfectant solution, characterized in that it hasa pH of between 10.1 and 10.7 and comprises from 0.021 to 5.76% (w/v) ofsodium hypochlorite and, relative to the said amount of sodiumhypochlorite, not more than 2% of sodium chlorate.

Preferably, the amount of sodium hypochlorite included in thedisinfectant solution of the present invention ranges from 0.52% to2.09% (w/v), equivalent to 0.50–2.00% of active chlorine.

Advantageously, the pH of the disinfectant solution of the presentinvention is between 10.1 and 10.5.

Typically, the disinfectant solution of the present invention whichcomprises from 0.021 to 5.76% (w/v) of sodium hypochlorite, alsocomprises from 0.015 to 4% (w/v) of sodium chloride.

The disinfectant solution of the present invention may be readily madeisotonic by adding a suitable amount of sodium chloride.

In addition, a suitable amount of a colorant that is compatible with thecomponents of the solution may also be added to the disinfectantsolution of the present invention. A typical example of a suitablecolorant is potassium permanganate.

The addition of dilute hydrochloric acid to pH 10.1–10.7 is sufficientto obtain a hypochlorite disinfectant solution that has all theadvantages that will be listed hereinbelow. However, after the pH hasbeen partially corrected with dilute hydrochloric acid, for example to11, a small amount of another compound capable of correcting the pH, forexample from 11 to 10.5, may be added. Typical examples of suchcompounds are: sodium tetraborate, sodium bicarbonate, sodium carbonate,sodium monohydrogen phosphate, sodium dihydrogen phosphate and the like.

In a second aspect thereof, the present invention relates to a processfor preparing a sodium hypochlorite disinfectant solution, in which thesaid process comprises the dilution of a concentrated sodiumhypochlorite solution, characterized in that the pH of this solution isbrought to a value of between 10.1 and 10.7 by adding dilutehydrochloric acid.

Typically, before being subjected to the process of the presentinvention, the concentrated solution comprises from 15.70 to 20.93%(w/v) of sodium hypochlorite and its pH is about 13.

Preferably, the concentration of hydrochloric acid in the dilutesolution used in the process of the present invention ranges from 0.01to 1 mol/liter and preferably 0.1–1 mol/liter.

The sodium hypochlorite disinfectant solution according to the presentinvention has the following advantages;

-   -   it is economical since it is readily and quickly prepared by        means of very simple apparatus;    -   it is well tolerated like Dakin's solution and the other        analogous solutions described in the pharmacopoeias and like the        electrolytic solutions;    -   it is stable like electrolytic solutions and is therefore        suitable for sale in pharmacies as a ready-to-use solution;    -   it is readily adaptable to various requirements in terms of        concentrations and addition of other solutes;    -   it has high bactericidal efficacy; and    -   it contains very small amounts of sodium chlorate.

The examples which follow serve to illustrate the invention without,however, limiting it.

EXAMPLE 1 Solution 1

750 ml of distilled water were added to 58.97 ml of a solution,containing 19.5% (w/v) of sodium hypochlorite, 18% (w/v) of sodiumchloride and less than 10 ppm of sodium chlorate, and having a pH of 13.

1N HCl was then added until the pH was 10.5.

Finally, distilled water was added to make 1000 ml.

The solution thus obtained contained 1.15% (w/v) of sodium hypochlorite[equivalent to 1.1% (w/v) of active chlorine] and 1.06% (w/v) of sodiumchloride.

EXAMPLES 2–3 Solutions 2 and 3

To check the effect of the pH correctors, the process was performedexactly as described in Example 1, except that the pH of the startingsolution was first brought to 11 with 1N HCl and then to 10.5 withsodium tetraborate (Solution 2) or sodium bicarbonate (Solution 3).

EXAMPLE 4 Solution 4

To check the effect of the sodium chloride, the process was performedexactly as described in Example 1, except that the content of sodiumchloride was then raised to 18% (w/v).

TEST 1 Stability

The stability of Solutions 1–4 was studied for 75 days in an environmenthaving a temperature of 40° C. and a relative humidity of 75% and for 63days at ambient temperature (about 24° C.).

The study was performed in comparison with an electrolytic solution(Comparative Solution) of pH 10.3 and containing 1.15% (w/v) of sodiumhypochlorite (equivalent to 1.1% of active chlorine), 18% sodiumchloride and, relative to the abovementioned amount of sodiumhypochlorite, about 26% (w/v) of sodium chlorate.

The results are illustrated in Tables I and II below.

TABLE I (T = 40° C.; R.H. = 75%) Solution PH Sodium hypochloriteChlorates (ppm) No. initial 75 days initial 75 days initial 75 days 110.5 10.1 1.15 0.98 162 1046 2 10.5 10.1 1.15 0.90 134 1413 3 10.5 10.21.15 0.93 146 1272 4 10.5 9.8 1.15 0.85 157 1548 Comparative 10.3 9.61.15 0.80 2640 4128

TABLE II (Ambient temperature) Solution PH Sodium hypochlorite Chlorates(ppm) No. initial 63 days initial 63 days initial 63 days 1 10.5 10.31.15 1.14 162 251 2 10.5 10.4 1.15 1.15 134 281 3 10.5 10.4 1.15 1.14146 272 4 10.5 10.4 1.15 1.15 157 295 Comparative 10.3 10.2 1.15 1.112640 2950

These data prove that the disinfectant solution of the present inventionbehaves like the comparative electrolytic solution which, as is known,is stable for at least 2 years. Thus, it may reasonably be deduced thatthe solution of the invention will also be stable for at least twoyears.

TEST 2 Bactericidal Activity

The bactericidal activity of the disinfectant solution of Example 1 wascompared with that of the electrolytic solution mentioned in thepreceding Test 1, according to standard UNI EN 1040.

Strains of Staphylococcus aureus ATCC 6538 and Pseudomonas aeruginosaATCC 15442 were subjected, for 5 minutes at 20° C., to solutionscontaining five different concentrations of sodium hypochlorite,respectively: 28.75 ppm, 57.5 ppm, 115 ppm, 230 ppm and 460 ppm,obtained by diluting the solutions under investigation.

The interpretation of the results according to standard UNI EN 1040showed that both the solutions induce a logarithmic reduction >10⁵ inthe bacterial vitality.

In conclusion, the two solutions under investigation showed themselvesto have the same bactericidal activity at the same concentrations.

1. A sodium hypochlorite disinfectant solution, comprising: 0.021 to5.76% (w/v) of sodium hypochlorite, from 0.015 to 4% (w/v) of sodiumchloride, and water; wherein the solution is buffer-free and contains nomore than 2% of sodium chlorate relative to the sodium hypochlorite; andwherein the solution has a pH that ranges from 10.1 to 10.7.
 2. Thesolution according to claim 1, wherein the sodium hypochlorite rangesfrom 0.52% to 2.09% (w/v).
 3. The solution according to claim 1 or claim2, wherein the pH is between 10.1 and 10.5.
 4. The solution according toclaim 1 or claim 2, further comprising a colorant.
 5. The solutionaccording to claim 3, further comprising a colorant.
 6. A process forpreparing the sodium hypochlorite disinfectant solution as claimed inclaim 1, which comprises: diluting a concentrated sodium hypochloritesolution to obtain a dilute sodium hypochlorite solution and addingdilute hydrochloric acid to the dilute sodium hypochlorite solution toobtain the sodium hypochlorite disinfectant solution having a pH between10.1 and 10.7.
 7. The process according to claim 6, wherein theconcentrated hypochlorite solution has a pH of 13 and comprises from15.70 to 20.93% (w/v) of sodium hypochlorite.
 8. The process accordingto claim 6 or claim 7, wherein the dilute hydrochloric acid solutioncomprises 0.01–1 mol/liter of hydrochloric acid.